NQO1 gene expression was evaluated by RT-PCR and SNP status by RFLP in matched samples of lung tumors and adjacent normal tissue. NQO1 was found to be overexpressed in lung tumors when compared to matched normal lung tissue. The mean expression in normal lung tissue was 28.26 x 10(-14) ng/microl +/- 44.9 SD and 61.46 x 10(-14) ng/microl +/- 103.2 SD in lung tumors. NQO1 gene expression was higher in the tumor than in the matched normal lung tissue in 27/50 (59%) patients (p=0.014). In the normal samples, 25 (50%) were wild-type, 16 were heterozygotes (32%) and 8 had the SNP (16%). In the matched tumor samples 14 were wild-type (28%), 16 were heterozygous (32%) and 19 (38%) had the SNP (p=0.0043). The genomic NQO1 mutation was associated with survival in a pilot study of stage II/III NSCLC patients. Patients with a homozygous SNP genotype had a significantly shorter survival (median 12 months), than heterozygous or homozygous wild-type patients (median 41 months) (p=0.007), suggesting NQO1 may be important in chemosensitivity as well as the pathogenesis of lung cancer and NQO1 genotyping may be a useful component of pharmacogenetic strategies for the treatment of NSCLC.